LOS Groups Research Articles

Gut microbiota in preterm infants with late-onset sepsis and pneumonia: a pilot case-control study

BackgroundLate-onset sepsis (LOS) and pneumonia are common infectious diseases, with high morbidity and mortality in neonates. This study aimed to investigate the differences in the gut microbiota among preterm infants with LOS, or pneumonia, and full-term infants. Furthermore, this study aimed to determine whether there is a correlation between intestinal pathogenic colonization and LOS.MethodsIn a single-center case‒control study, 16 S rRNA gene sequencing technology was used to compare gut microbiota characteristics and differences among the LOS group, pneumonia group, and control group.ResultsOur study revealed that the gut microbiota in the control group was more diverse than that in the LOS group and pneumonia group (P < 0.05). No significant differences in diversity were detected between the LOS and pneumonia groups (P > 0.05). Compared with the control group, the abundances of Akkermansia, Escherichia/Shigella, and Enterococcus increased, while the abundances of Bacteroides and Stenotrophomonas decreased in the LOS and pneumonia groups. The pathogenic bacteria in infants with LOS were consistent with the distribution of the main bacteria in the intestinal microbiota. An increase in Escherichia/Shigella abundance may predict a high risk of LOS occurrence, with an area under the curve (AUC) of 0.773.ConclusionChanges in the gut microbiota composition were associated with an increased risk of LOS and pneumonia. The dominant bacteria in the gut microbiota of the LOS group were found to be associated with the causative pathogen of LOS. Moreover, preterm infants exhibiting an elevated abundance of Escherichia/Shigella may be considered potential candidates for predicting the onset of LOS.

The Association between Preoperative Blood Pressure Elevations and Postoperative Adverse Outcomes after Non-cardiac Surgery: A Single-center Retrospective Observational Study.

Blood pressure (BP) often rises before surgery. This study investigated whether BP elevation immediately before surgery was associated with adverse outcomes. Medical records of 11,732 patients (average age: 61 years; male: 47.4%) who underwent non-cardiac elective inpatient surgery under general anesthesia at Kagawa University Hospital between January 2011 and June 2019 were reviewed. Differences between the first BP values measured on the day before surgery and the first BP values in the operating room were defined as Δ systolic BP (ΔSBP) and Δ diastolic BP (ΔDBP). The relationships between ΔSBP/ΔDBP and 30-day mortality, 30-day readmission, and over-the-standard length of hospital stay (OSLOS) were assessed. OSLOS was defined as a hospital stay longer than mean+2 standard deviations and was calculated using the Japanese Diagnosis Procedure Combination data. In univariate analysis, the differences in ΔSBP and ΔDBP between the OSLOS and standard LOS groups were both 2 mmHg. In multivariate logistic regression analysis, only ΔDBP was associated with OSLOS. The adjusted odds ratio (95% confidence interval) for the largest quartile was 1.31 (1.02-1.69) (p<0.05). ΔDBP was associated with OSLOS; however, there may be little need to worry about large ΔSBPs and ΔDBPs in clinical practice.

Raspberry Supplementation Attenuates Blood Pressure and Improves Mesenteric Artery Relaxation in a Nitric Oxide-Independent Mechanism in Angiotensin II-Treated Rats

ObjectivesBerries are rich in polyphenols with strong antioxidant capacity. They have been suggested to exert antihypertensive properties, which may be due to an increase in the levels of endothelial nitric oxide (NO), a potent vasodilator. Thus, the objective of this study was to evaluate the effects of raspberry supplementation on vascular function in angiotensin (Ang) II-treated rats. MethodsEight-week-old Sprague-Dawley rats (n = 8/group) were fed an AIN-93M diet (control, Ang II, and Losartan (LOS; 20 mg/kg/BW) groups) or AIN-93M diet supplemented with 10% w/w freeze-dried raspberry (RB + Ang II) for 7 weeks. At week 5, rats were implanted with subcutaneous osmotic minipumps that delivered 0.9% saline (CON) or Ang II (270 ng/kg BW/min) for an additional 3 weeks. Blood pressure (BP) was measured using tail-cuff plethysmography (n = 7–8/group). First order mesenteric arteries were isolated for vascular relaxation measurements following constriction by U46619 (1 μM) in a wire myograph (n = 3–8/group). Data were found to be normal and analyzed using ANOVA or mixed-model where appropriate. ResultsAng II group showed a significant increase in systolic BP (SBP) (+26.8%, p = 0.002) 2 weeks after implantation as compared to baseline, while CON, RB + Ang II, and LOS groups showed no differences. Final SBP was significantly lower in the CON (–26.4%, p = 0.01), LOS (–28.3%, p = 0.0005), and RB + Ang II (–20.8%, p = 0.03) groups compared to Ang II group. Relaxation was significantly inhibited in the Ang II group in the presence of acetylcholine after incubation with L-NAME (100 μM), a NO synthase inhibitor, when compared to LOS (p = 0.0003) and RB + Ang II (p = 0.0004) groups. Similarly, relaxation in the Ang II group was significantly inhibited after incubation with ODQ (10 μM), a sGC inhibitor, when compared to CON (p = 0.0002), LOS (p = 0.0004), and RB + Ang II (p = 0.0001) group. No significant changes in vessel relaxation were observed after incubation with LY294002 (20 μM), a PI3K inhibitor. ConclusionsWe demonstrate that RB supplementation attenuated Ang II-induced hypertension and abolished the inhibitory effects of L-NAME and ODQ. This suggests that RB may exert its vasodilatory effects in a NO-independent manner. Funding SourcesThe Agriculture and Food Research Initiative (grant no. 2019–67,017-29,257/project accession no. 1,018,642) from the USDA National Institute of Food and Agriculture.

Prolonged length of stay in acute psychiatric wards: A descriptive study

IntroductionThe psychiatric care paradigm has shifted towards community-centered models. Yet, prolonged hospitalizations are still a reality, with debated impact at healthcare systems and patients.ObjectivesThis work aims to describe prolonged hospitalizations in acute psychiatric wards through patients’ sociodemographic and clinical data.MethodsWe analyzed a national hospitalization database that contained all hospitalization episodes registered in Portuguese public hospitals from 2008 to 2015. All episodes with a primary diagnosis of mental disorder defined as ICD-9-CM codes 290.x-319.x were included. Prolonged hospitalizations were defined as having a LoS ≥ P97.5; LOS ≥180 days or LOS ≥1 year. Age, sex, lengh of stay, in-hospital mortality were analysed.ResultsThe LoS ≥ P97.5(≥62 days) group comprised 3911 hospitalizations (2.3% of all psychiatric hospitalizations) and 1755 patients. The median LOS was 81 days and the mean age was 51 years. Sex was equally distributed, though a higher frequency of male patients was found on the ≥180 days (n=364) and ≥ 1 year (n=121) groups. Psychotic disorders were the main diagnosis at discharge (n= 1769, 45.2%), followed by mood disorders (n=1057, 27.0%) and dementia (n=451, 11.5%). In-hospital mortality increased in the higher LoS groups (1.1%; 4.4%; 9.1%, respectively).ConclusionsOverall, middle aged patients with psychotic disorders represent most of the prolonged hospitalizations occurring in acute psychiatric wards. Community-based programs require further development to meet the existing needs.DisclosureNo significant relationships.

Peripheral chemoresponsiveness during exercise in male athletes with exercise‐induced arterial hypoxaemia

What is the central question of this study? Do highly trained male endurance athletes who develop exercise-induced arterial hypoxaemia (EIAH) demonstrate reduced peripheral chemoresponsiveness during exercise? What is the main finding and its importance? Those with the lowest arterial saturation during exercise have a smaller ventilatory response to hypercapnia during exercise. There was no significant relationship between the hyperoxic ventilatory response and EIAH. The findings suggest that peripheral chemoresponsiveness to hypercapnia during exercise could play a role in the development of EIAH. The findings improve our understanding of the mechanisms that contribute to EIAH. Exercise-induced arterial hypoxaemia (EIAH) is characterized by a decrease in arterial oxygen tension and/or saturation during whole-body exercise, which may in part result from inadequate alveolar ventilation. However, the role of peripheral chemoresponsiveness in the development of EIAH is not well established. We hypothesized that those with the most severe EIAH would have an attenuated ventilatory response to hyperoxia and hypercapnia during exercise. To evaluate this, on separate days, we measured ventilatory sensitivity to hyperoxia and separately hypercapnia at rest and during three different exercise intensities (25, 50% of and ventilatory threshold (∼67% of )) in 12 males cyclists ( =66.6±4.7mlkg-1 min-1 ). Subjects were divided into two groups based on their end-exercise arterial oxygen saturation (ear oximetry, ): a normal oxyhaemoglobin saturation group (NOS, =93.4±0.4%,n=5) and a low oxyhaemoglobin saturation group (LOS, =89.9±0.9%, n=7). There was no difference in (66.4±2.9vs.66.8±6.0mlkg-1 min-1 , respectively, P=0.9), peak ventilation during maximal exercise (182±15vs.197±32lmin-1 , respectively, P=0.36) or ventilatory response to hyperoxia (P=0.98) at any exercise intensity between NOS and LOS groups. However, those in the LOS group had a significantly lower ventilatory response to hypercapnia (P=0.004, (η2 =0.18). There was also a significant relationship between the mean hypercapnic response and end-exercise (r=0.75, P=0.009) but not between the mean hyperoxic response and end-exercise (r=0.21, P=0.51). A blunted hypercapnic ventilatory response may contribute to EIAH in highly trained men due to a failure to increase ventilation sufficiently to offset exercise-induced gas exchange impairments.

83 - Effects of losartan on experimental varicocele-induced testicular germ cell apoptosis

Summary To investigate the potential protective effects of losartan on varicocele-induced germ cell apoptosis, 24 adult male Sprague Dawley rats were divided into three groups: a sham operation was performed in SHAM group, and experimental left varicocele was created in VAR and VAR + LOS groups. Additionally, in VAR + LOS group, losartan was administered for 30 days starting on the day of surgery. At the end of 30 days, all animals were sacrificed and left orchiectomy was performed. Testicular injury and spermatogenesis were evaluated according to Johnsen scoring system. To assess the nitrosative stress, immunohistochemical staining for endothelial nitric oxide synthase was used and evaluated by H-score and apoptotic index (AI) of germ cells was analysed by TUNEL method. A significant decrease in the mean Johnsen score (JS) was observed in VAR group compared with SHAM (p < .001). The mean H-score and AI were significantly higher in VAR group compared with SHAM (p < .001). After losartan administration, mean JS was significantly increased (p < .001) and mean H-score and AI were significantly decreased compared with VAR group (p < .001 and .01, respectively). Findings of this suggest that losartan acts as a potent protective agent against varicocele-induced germ cell apoptosis.

Novel mechanism of intra‑renal angiotensin II-induced sodium/proton exchanger 3 expression by losartan in spontaneously hypertensive rats.

The present study aimed to investigate the molecular pharmacodynamic mechanisms of losartan used in the treatment of hypertension. A total of 12 spontaneously hypertensive rats (SHR) were divided randomly into an SHR group treated with saline and LOS group treated with losartan. Six Wistar‑kyoto rats (WKY) were enrolled as the WKY group with saline in the study. The LOS group received 30mg/kg/day losartan by intragastric injection, while the SHR and WKY were fed the same volume of saline. The dosage was modulated according to the weekly weight. Changes in blood pressure were measured by the indirect tail cuff method. Angiotensin (Ang) II production in the plasma and renal tissue was measured by an immunoradiometric method. Na+/H+ exchanger (NHE)3 and serum and glucocorticoid‑inducible kinase (SGK)1 were assessed by quantitative polymerase chain reaction (qPCR) and western blot analysis. When compared with the WKY group, the blood pressure of the SHR and LOS groups were higher prior to treatment with losartan. Following two weeks, blood pressure was reduced and the trend continued to decrease over the following six weeks. The plasma and renal tissue levels of Ang II in the SHR and LOS groups were significantly higher than those in the WKY group. NHE3 and SGK1 were increased at the mRNA and protein level in the SHR group, and losartan reduced the expression of both of them. The results suggested that in hypertensive rats, the circular and tissue renin angiotensin systems were activated, and the increased Ang II stimulated the expression of NHE3 and SGK1, which was reduced by losartan. Therefore, the effects of losartan in hypertension may be associated with the AngII‑SGK1‑NHE3 of intra‑renal tissue.

Impaired endocytosis in proximal tubule from subchronic exposure to cadmium involves angiotensin II type 1 and cubilin receptors

BackgroundChronic exposure to low cadmium (Cd) levels produces urinary excretion of low molecular weight proteins, which is considered the critical effect of Cd exposure. However, the mechanisms involved in Cd-induced proteinuria are not entirely clear. Therefore, the present study was designed to evaluate the possible role of megalin and cubilin (important endocytic receptors in proximal tubule cells) and angiotensin II type 1 (AT1) receptor on Cd-induced microalbuminuria.MethodsFour groups of female Wistar rats were studied. Control (CT) group, vehicle-treated rats; LOS group, rats treated with losartan (an AT1 antagonist) from weeks 5 to 8 (10 mg/kg/day by gavage); Cd group, rats subchronically exposed to Cd (3 mg/kg/day by gavage) during 8 weeks, and Cd + LOS group, rats treated with Cd for 8 weeks and LOS from weeks 5–8. Kidney Cd content, glomerular function (evaluated by creatinine clearance and plasma creatinine), kidney injury and tubular function (evaluated by Kim-1 expression, urinary excretion of N-acetyl-β-D-glucosaminidase (NAG) and glucose, and microalbuminuria), oxidative stress (measured by lipid peroxidation and NAD(P)H oxidase activity), mRNA levels of megalin, expressions of megalin and cubilin (by confocal microscopy) and AT1 receptor (by Western blot), were measured in the different experimental groups. Data were analyzed by one-way ANOVA or Kruskal-Wallis test using GraphPad Prism 5 software (Version 5.00). P < 0.05 was considered statistically significant.ResultsAdministration of Cd (Cd and Cd + LOS groups) increased renal Cd content. LOS-treatment decreased Cd-induced microalbuminuria without changes in: plasma creatinine, creatinine clearance, urinary NAG and glucose, oxidative stress, mRNA levels of megalin and cubilin, neither protein expression of megalin nor AT1 receptor, in the different experimental groups studied. However, Cd exposure did induce the expression of the tubular injury marker Kim-1 and decreased cubilin protein levels in proximal tubule cells whereas LOS-treatment restored cubilin levels and suppressed Kim-1 expression.ConclusionLOS treatment decreased microalbuminuria induced by Cd apparently through a cubilin receptor-dependent mechanism but independent of megalin.

Inhalation delivery of Telmisartan enhances intratumoral distribution of nanoparticles in lung cancer models

The purpose of the present study was to evaluate the effect of Telmisartan (Tel) and Losartan (Los) on nanoparticle intratumoral distribution and anticancer effects in lung cancer. A549 lung tumor cells were orthotopically and metastatically administered to Nu/nu mice. Fluorescent polystyrene nanoparticles (FPNPs, size ~200nm) beads were used to study their intratumoral distribution after Tel and Los treatments. Animals were administered with FPNPs and after 2h, FPNPs intratumoral distribution was studied by fluorescent microscopy. Tel (~1.12mg/kg) and Los (~4.5mg/kg) were administered by inhalation delivery at alternative days for 4weeks to tumor bearing animals. Collagen-1, transforming growth factor beta 1 (TGF-β1), cleaved caspase-3, Vimentin and E-Cadherin expressions were studied by western blotting. To correlate the AT1 receptor blockage to anticancer effects, VEGF levels and microvessel densities (MVD) were quantified. Los and Tel treated group resulted in the 5.33 and 14.33 fold increase respectively in the FPNPs intratumoral distribution as compared to the controls. Tel treatment attenuated 2.23 and 1.70 fold Collagen 1 expression compared to untreated control and Los groups, respectively. Further, in Tel and Los treated groups, the TGF-β1 active levels were significantly (p<0.05) decreased. Tel (at four times less dose) was 1.89 and 1.92 fold superior in anticancer activity to Los respectively in A549 orthotopic and metastatic tumor models (p<0.05) when given by inhalation route. Tel, by virtue of its dual pharmacophoric nature could be an ideal candidate for combination therapy to improve the nanoparticle intratumoral distribution and anticancer effects.

Resistin—A Novel Feature in the Diagnosis of Sepsis in Premature Neonates

To evaluate the diagnostic potential of resistin in sepsis and to compare results with C-reactive protein (CRP) in infants < 32 weeks of gestation. A total of 64 infants were prospectively included in the study. Blood samples were collected for basal CRP and resistin within the first hour of life. When sepsis was suspected, samples were collected for CRP and resistin before the treatment was started (pretreatment CRP and resistin). On the third day of sepsis, CRP and resistin levels were measured for evaluating the treatment response (follow-up CRP and follow-up resistin). Culture-proven septic patients were divided into groups according to early or late-onset sepsis (EOS and LOS) and gram-negative or gram-positive sepsis (GNS and GPS). Pretreatment and follow-up resistin levels were significantly higher than basal resistin levels in both EOS and LOS groups (p < 0.01), with a positive correlation with CRP levels. To predict the GNS and GPS area under curve, values of pretreatment CRP and resistin were 0.714 and 0.984, respectively (p = 0.039). Resistin had a superior potential to that of CRP in the diagnosis of sepsis in preterm infants. Resistin may be used as an early marker for sepsis in premature infants.

The role of AT1 receptor-mediated reproductive function in renovascular hypertension in male rats

There is an association between hypertension and reproductive dysfunction. Angiotensin II (Ang II) is involved in the pathogenesis of hypertension and the regulation of reproduction. The present study aimed to determine whether the angiotensinergic system mediates the effects of hypertension on reproductive function in male rats subjected to a two-kidney, one-clip (2K1C) model. Sexual behavior parameters, gametogenesis and plasma concentrations of Ang II, testosterone, prolactin and corticosterone were evaluated in male rats 28days after 2K1C or sham surgery and losartan (Los) treatment (a type 1 angiotensin II (AT1) receptor antagonist) or vehicle (V) treatment. The animals were divided into Sham+V, 2K1C+V, Sham+Los and 2K1C+Los groups. The 2K1C+V group showed a hypertensive response, inhibition of sexual behavior, spermatogenesis dysfunction, and increases in plasma Ang II and prolactin. Conversely, plasma testosterone decreased, and plasma corticosterone remained constant. Losartan treatment normalized blood pressure and prevented the changes in plasma testosterone and prolactin, sexual behavior and spermatogenesis in the 2K1C+Los group. In addition, losartan treatment caused an additional increase in circulating Ang ll in both groups (Sham+Los and 2K1C+Los). Together, these results suggest that Ang ll, acting through the AT1 receptor, modulates behavioral and endocrine parameters of reproductive function during renovascular hypertension. In addition, the effects of circulating Ang II on plasma testosterone and prolactin seem to contribute to the spermatogenic and sexual dysfunctions in hypertensive rats.

Salt-Induced Cardiac Hypertrophy and Interstitial Fibrosis Are Due to a Blood Pressure–Independent Mechanism in Wistar Rats1–3

High salt intake is a known cardiovascular risk factor and is associated with cardiac alterations. To better understand this effect, male Wistar rats were fed a normal (NSD: 1.3% NaCl), high 4 (HSD4: 4%), or high 8 (HSD8: 8%) salt diet from weaning until 18 wk of age. The HSD8 group was subdivided into HSD8, HSD8+HZ (15 mg.kg−1.d−1 hydralazine in the drinking water), and HSD8+LOS (20 mg.kg−1.d−1 losartan in the drinking water) groups. The cardiomyocyte diameter was greater in the HSD4 and HSD8 groups than in the HSD8+LOS and NSD groups. Interstitial fibrosis was greater in the HSD4 and HSD8 groups than in the HSD8+HZ and NSD groups. Hydralazine prevented high blood pressure (BP) and fibrosis, but not cardiomyocyte hypertrophy. Losartan prevented high BP and cardiomyocyte hypertrophy, but not fibrosis. Angiotensin II type 1 receptor (AT1) protein expression in both ventricles was greater in the HSD8 group than in the NSD group. Losartan, but not hydralazine, prevented this effect. Compared with the NSD group, the binding of an AT1 conformation-specific antibody that recognizes the activated form of the receptor was lower in both ventricles in all other groups. Losartan further lowered the binding of the anti-AT1 antibody in both ventricles compared with all other experimental groups. Angiotensin II was greater in both ventricles in all groups compared with the NSD group. Myocardial structural alterations in response to HSD are independent of the effect on BP. Salt-induced cardiomyocyte hypertrophy and interstitial fibrosis possibly are due to different mechanisms. Evidence from the present study suggests that salt-induced AT1 receptor internalization is probably due to angiotensin II binding.

Is late‐onset schizophrenia a subtype of schizophrenia?

To determine whether late-onset schizophrenia (LOS, onset after age 40) should be considered a distinct subtype of schizophrenia. Participants included 359 normal comparison subjects (NCs) and 854 schizophrenia out-patients age >40 (110 LOS, 744 early-onset schizophrenia or EOS). Assessments included standardized measures of psychopathology, neurocognition, and functioning. Early-onset schizophrenia and LOS groups differed from NCs on all measures of psychopathology and functioning, and most cognitive tests. Early-onset schizophrenia and LOS groups had similar education, severity of depressive, negative, and deficit symptoms, crystallized knowledge, and auditory working memory, but LOS patients included more women and married individuals, had less severe positive symptoms and general psychopathology, and better processing speed, abstraction, verbal memory, and everyday functioning, and were on lower antipsychotic doses. Most EOS-LOS differences remained significant after adjusting for age, gender, severity of negative or deficit symptoms, and duration of illness. Late-onset schizophrenia should be considered a subtype of schizophrenia.

Chronic AT1receptor blockade normalizes NMDA-mediated changes in renal sympathetic nerve activity and NR1expression within the PVN in rats with heart failure

Exercise training normalizes enhanced glutamatergic mechanisms within the paraventricular nucleus (PVN) concomitant with the normalization of increased plasma ANG II levels in rats with heart failure (HF). We tested whether ANG II type 1 (AT(1)) receptors are involved in the normalization of PVN glutamatergic mechanisms using chronic AT(1) receptor blockade with losartan (Los; 50 mg.kg(-1).day(-1) in drinking water for 3 wk). Left ventricular end-diastolic pressure was increased in both HF + vehicle (Veh) and HF + Los groups compared with sham-operated animals (Sham group), although it was significantly attenuated in the HF + Los group compared with the HF + Veh group. The effect of Los on cardiac function was similar to exercise training. At the highest dose of N-methyl-d-aspartate (NMDA; 200 pmol) injected into the PVN, the increase in renal sympathetic nerve activity was 93 +/- 13% in the HF + Veh group, which was significantly higher (P < 0.05) than the increase in the Sham + Veh (45 +/- 2%) and HF + Los (47 +/- 2%) groups. Relative NMDA receptor subunit NR(1) mRNA expression within the PVN was increased 120% in the HF + Veh group compared with the Sham + Veh group (P < 0.05) but was significantly attenuated in the HF + Los group compared with the HF + Veh group (P < 0.05). NR(1) protein expression increased 87% in the HF + Veh group compared with the Sham + Veh group but was significantly attenuated in the HF + Los group compared with the HF + Veh group (P < 0.05). Furthermore, in in vitro experiments using neuronal NG-108 cells, we found that ANG II treatment stimulated NR(1) protein expression and that Los significantly ameliorated the NR(1) expression induced by ANG II. These data are consistent with our hypothesis that chronic AT(1) receptor blockade normalizes glutamatergic mechanisms within the PVN in rats with HF.

Angiotensin II (ANG II) does not utilize the Janus Kinase 2/Signal Transducers of Activated Transcription (JAK/STAT) pathway in the molecular mechanism of blood pressure response to a low salt diet

We recently reported that the JAK2 inhibitor AG490 prevented JAK/STAT pathway activation and hypertension during chronic iv. ANG II infusion. It is unknown, however, whether activation of JAK2 is required for ANG II to prevent blood pressure from decreasing in the physiologic response to low salt intake. This was tested by blocking JAK2 activation chronically in rats that were switched from normal‐ to low‐salt intake. Male SD rats with instrumented with artery and vein catheters for 24 hr/day mean arterial pressure (MAP) measurement and iv. infusions. Rats were maintained on a normal‐salt (NS) intake (~ 3 mEq/day), and after baseline measurements chronic iv. infusions of either: vehicle (Veh; saline), the AT1 receptor antagonist Losartan (LOS; 10 mg/kg/day) or AG490 (AG; 10 ng/kg/min) were begun. After a 4‐day control period, rats were switched to low‐salt intake (LS; 0.4 mEq/day), while Veh, LOS and AG infusions continued. There were no differences in MAP between any group under baseline conditions. During the control period, MAP averaged 93+4, 97+3 and 80+2 mm Hg in Veh, AG, and LOS groups, respectively. Switching to LS intake did not change MAP in Veh and AG rats (102+4 and 101+3 mm Hg, respectively); but MAP decreased significantly in LOS rats to 72+4 mm Hg by day 5. These data suggest that JAK2 activation is not involved in ANG II's role in the blood pressure response to LS intake. (HL74167 MWB; HL91177 AB)

Incidence and Etiology of Umbilical Infections in Newborns in Low-income Communities of Karachi, Pakistan

Results: During the 40-month study period, we identified 1,370 children with influenza including 966 (71%) inpatients. Among 1,368 patients with birth information, 490 (36%) were 10 days, there were twice as many episodes in children aged < 24 months (n = 30) compared with those in the rest of the age groups of patients combined (n = 15). The mean total direct cost associated with laboratory-confirmed influenza was $1,205. Stratified by LOS groups, the mean total direct cost for LOS of 1—5 days was $874 compared to that of $1415 for LOS of 6—10 days. The mean direct costs for treatment, testing, and admission were $319, $383, and $441, respectively. Conclusions: More than three-quarters of pediatric influenza occurred within the first five years of life. The economic burden of this disease in Korea suggests the need to consider inclusion of infants and toddler in annual routine influenza immunization program.

Sanguinarine Downregulates AT1a Gene Expression in a Hypertensive Rat Model

We studied the in vivo effects of sanguinarine in a hypertensive rat model and its effects on AT1a mRNA expression in kidney tissues. Rats received daily for 14 d sanguinarine 0.1 mg/kg (SangL) and 0.3 mg/kg (SangH), losartan 1 mg/kg by weight (Los), or DMSO (Con). Blood pressures were monitored regularly and urine volume and sodium concentration was measured on days 0, 7, and 14. On day 15, animals were anesthetized (sodium thiopentane, 50 mg/kg), blood samples for aldosterone levels were taken, and kidneys were removed for AT1a mRNA expression. Los and SangH groups showed reduced AT1a mRNA expressions by 4.22- and 5.9-fold, respectively. In the SangL group it was reduced by 2.7-fold. Decreases in systolic blood pressures mirrored decreases in AT1a mRNA expressions in all groups. Los and SangH groups showed reductions in systolic blood pressure of 12.3% and 19.3%, respectively, whereas in the SangL group, it was reduced by 8.07%. Urine output in the Los group increased (228% mean increase from days 0-14), whereas sodium excretion decreased by 69.6% (mean decrease from days 0-14). In the SangL and SangH groups, urine volumes increased significantly by 108.3% and 115% (mean increase from days 0-14), respectively. Urinary sodium excretion increased significantly by 60.9% in the SangH group. We concluded that sanguinarine reduces blood pressure in the Dahl rat because of decreased AT1 receptor expression and reduced aldosterone levels. The action of losartan on increased urinary volume and decreased sodium excretion may be attributed to reduced vasopressin secretion.

P50 sensory gating: Impact of high vs. low schizotypal personality and smoking status

Sensory gating deficits are seen in individuals with schizophrenia and schizotypal disorders, yet smoking influence, regional or lateral difference effects are rarely assessed. We examined sensory gating in smokers and non-smokers within university-level high and low schizotypal personality (HiS and LoS) groups using Raine's (1991) [Raine, A., 1991. The Schizotypal Personality Questionnaire (SPQ): A measure of schizotypal personality based on DSM-III-R criteria. Schizophr. Bull. 17, 555–564] Schizotypal Personality Questionnaire. Among 39 (18 men; 19 smokers) right-handed undergraduates, a paired-tone paradigm (40 pairs; 10 s ISI; 70 dB, 1000 Hz) was presented in two conditions (smokers while abstaining and after smoking). Sensory gating [S2(P50–N40)/S1(P50–N40)] was assessed at frontal, fronto-central, central, centro-parietal, and parietal midline and lateralized sites. Sensory gating was better at (1) midline than left/right hemispheric sites, and (2) fronto-central and central midline sites. At fronto-central/central lateral sites, (1) among non-smokers, better sensory gating occurred in LoS than HiS, (2) among smokers, better sensory gating occurred in HiS than LoS, and (3) among LoSs, smokers showed less sensory gating than non-smokers. No acute smoking effects emerged. Unlike schizophrenia studies, smoking did not impact sensory gating. Differences among smokers and non-smokers in LoS and HiS groups reinforce need to evaluate both smoking and schizotypal characteristics, as well as midline and lateral sites in anterior to posterior regions, in sensory gating studies.

O bloqueio do sistema renina-angiotensina atenua a remodelação cardíaca de ratos submetidos a estenose aórtica

To assess the role of the AT1 receptor blocker and the angiotensin-converting enzyme inhibitor in cardiac remodeling induced by aortic stenosis in rats. Wistar rats were divided into the following 4 groups: 1) C--control (n=13); 2) AoS--aortic stenosis (n=11); 3) LIS--AoS treated with lisinopril, 20 mg/kg/day (n=11); and 4) LOS--AoS treated with losartan, 40 mg/kg/day (n=9). The treatments were initiated 3 days before surgery. After 6 weeks, the animals underwent echocardiographic study, and quantification of the hydroxyproline (HOP) concentration and the left ventricular (LV) myocyte cross-sectional area (CSA). Aortic stenosis induced an increase in left ventricular wall thickness. The LIS and LOS groups showed no difference as compared with the control group. The AoS and LIS rats had greater left atrial diameters than the control rats did, while no difference was observed in the LOS animals. The AoS animals had greater values of shortening percentage than control animals did. This fact was modified with neither LIS nor LOS. The cross-sectional area of the animals in the AoS group was greater than that in the control group. However, treatment with LOS and LIS attenuated the AoS-induced increase in area. Aortic stenosis caused an increase in HOP concentration, while the LOS group showed no difference as compared with the control group. Blockade of the renin-angiotensin system with AT1 blocker and ACEI may attenuate the development of heart hypertrophy, but only the blockade of AT1 receptors attenuates left ventricular interstitial fibrosis.

Course of functional improvement after stroke, spinal cord injury, and traumatic brain injury

Bode RK, Heinemann AW. Course of functional improvement after stroke, spinal cord injury, and traumatic brain injury. Arch Phys Med Rehabil 2002;83:100-6. Objective: To examine functional improvement patterns of persons with stroke, traumatic brain injury (TBI), and spinal cord injury (SCI). Design: Statistical analysis of data from a multisite study evaluating rehabilitation outcomes. Setting: Eight inpatient rehabilitation facilities. Participants: A total of 314 consecutive admissions of persons with stroke, SCI, and TBI who received acute medical rehabilitation between 1994 and 1998. Intervention: Calibration of motor and cognitive items from the FIM™ instrument, grouping of cases by number of weeks of rehabilitation (length of stay [LOS] groups), and plotting of weekly averages across time. Main Outcome Measures: Weekly motor and cognitive functional status. Results: With the exception of cognitive functioning for persons with SCI, LOS was related to initial functional status, with patients with greater disability having longer LOS (eg, initial motor status for persons with stroke was 48.3 for those with a 2-week stay, 36.8 for a 6-week stay, with the averages between decreasing monotonically). With the exception of cognitive gains for person with TBIs, the amount of functional gain during rehabilitation was essentially the same for all LOS groups (eg, the overall average total motor gain for persons with SCI is 22.3, with no patterns of increase or decrease across LOS groups); however, the rate of improvement in motor (but not cognitive) functioning differed across LOS groups, with patients with shorter stays having the greater rates of improvement (eg, the overall average weekly motor gain for persons with SCI was 3.6, with the averages by LOS group monotonically decreasing from 6.4 for those with 4-week stays to 2.7 for those with 9-week stays). Conclusions: When examined separately for persons grouped by LOS, functional status improved linearly during the rehabilitation stay, with differences in rate of improvement depending on initial functional status. © 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation